CD138, which acts as a receptor for the extracellular matrix, is overexpressed on multiple myeloma (MM) cells and has been shown to influence MM cell development and/or proliferation. CD138 is also expressed on cells of ovarian carcinoma, kidney carcinoma, gall bladder carcinoma, breast carcinoma, prostate cancer, lung cancer, colon carcinoma cells and cells of Hodgkin's and non-Hodgkin's lymphomas, chronic lymphocytic leukemia (CLL) to name just a few.
The publications and other materials, including patents, used herein to illustrate the invention and, in particular, to provide additional details respecting the practice are incorporated by reference. For convenience, the publications are referenced in the following text by author and date and/or are listed alphabetically by author in the appended bibliography.
Tassone et al. (2004) have reported excellent binding of the murine IgG1 antibody B-B4 to the CD138 antigen expressed on the surface of MM cells. Tassone also reported high cytotoxic activity of the immunoconjugate B-B4-DM1, which comprises the maytansinoid DM1 as an effector molecule, against multiple myeloma cells (see also US Patent Publ. 20070183971).
While Tassone et al. have contributed to providing an effective treatment of MM and a composition of matter that may be employed in such a treatment, there remain a number of needs in the art.
There remains a need for immunoconjugates based on B-B4 that are devoid of certain properties and/or functions associated with B-B4. There is, in particular a need for a chimerized antibody based on B-B4 that binds the CD138 as effectively as B-B4 but can be administered to humans without significant side effects. There is also a need for such a B-B4 based immunoconjugate that shows one or more advantageous properties relative to its murine counterpart. Those properties include improved antigen binding, improved killing of tumor cells comprising, in particular of CD138 expressing tumor cells, and cells accessory thereto or more homogenous binding of the target.